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Supplementary Figure 1 from Colorectal Cancer Cell Lines Are Representative Models of the Main Molecular Subtypes of Primary Cancer

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posted on 2023-03-30, 22:48 authored by Dmitri Mouradov, Clare Sloggett, Robert N. Jorissen, Christopher G. Love, Shan Li, Antony W. Burgess, Diego Arango, Robert L. Strausberg, Daniel Buchanan, Samuel Wormald, Liam O'Connor, Jennifer L. Wilding, David Bicknell, Ian P.M. Tomlinson, Walter F. Bodmer, John M. Mariadason, Oliver M. Sieber

PDF file - 137KB, Correlation between RNA-Seq and gene expression microarray data (Affymetrix U133 Plus2.0 Arrays) for six CRC cell lines analyzed in independent experiments. Genes with detectable expression on both platforms were considered, defined as RNA-Seq RPKM value >1 and microarray intensity > log2(100). r-values, Spearman's rank correlation coefficient.

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ARTICLE ABSTRACT

Human colorectal cancer cell lines are used widely to investigate tumor biology, experimental therapy, and biomarkers. However, to what extent these established cell lines represent and maintain the genetic diversity of primary cancers is uncertain. In this study, we profiled 70 colorectal cancer cell lines for mutations and DNA copy number by whole-exome sequencing and SNP microarray analyses, respectively. Gene expression was defined using RNA-Seq. Cell line data were compared with those published for primary colorectal cancers in The Cancer Genome Atlas. Notably, we found that exome mutation and DNA copy-number spectra in colorectal cancer cell lines closely resembled those seen in primary colorectal tumors. Similarities included the presence of two hypermutation phenotypes, as defined by signatures for defective DNA mismatch repair and DNA polymerase ϵ proofreading deficiency, along with concordant mutation profiles in the broadly altered WNT, MAPK, PI3K, TGFβ, and p53 pathways. Furthermore, we documented mutations enriched in genes involved in chromatin remodeling (ARID1A, CHD6, and SRCAP) and histone methylation or acetylation (ASH1L, EP300, EP400, MLL2, MLL3, PRDM2, and TRRAP). Chromosomal instability was prevalent in nonhypermutated cases, with similar patterns of chromosomal gains and losses. Although paired cell lines derived from the same tumor exhibited considerable mutation and DNA copy-number differences, in silico simulations suggest that these differences mainly reflected a preexisting heterogeneity in the tumor cells. In conclusion, our results establish that human colorectal cancer lines are representative of the main subtypes of primary tumors at the genomic level, further validating their utility as tools to investigate colorectal cancer biology and drug responses. Cancer Res; 74(12); 3238–47. ©2014 AACR.

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